These studies focus upon identifying nutritional or environmental factors inherent in Western culture which contribute to the high risk of colonic carcinoma. Emphasis is placed upon the role of the microbial flora in the modification of procarcinogens to carcinogens in the gut and the subsequent development of colonic carcinoma in humans. In this proposal, an experimental model, the rat, is utilized and fed a procarcinogen, 1,2 dimethylhydrazine (DMH). While DMH is not a common food or environmental contaminant, it shares a pathway in common with other known, or suspected, as well as presumably unknown procarcinogens, namely: 1) absorption from the gut; 2) modification or partial degradation and glucuronide formation with the liver; 3) excretion in the bile and 4) activation in the colon by bacterial populations which possess Beta-glucuronidases. Participation of the gut flora will be evaluated by determining the efficacy of DMH on colonic tumor induction in germ free rats whose intestinal morphology and immune system have been rendered "mature". In conventional animals, diets containing low normal and high levels of polyunsaturated or saturated fat are assessed for their ability to modify the effects of DMH on colonic tumor induction. Thus, the type of dietary fat which contributes to or diminishes the incidence of colonic carcinomata from ingested procarcinogens participating in an entero-hepatic circulation, may be delineated. Correlative studies of quantitative changes in the various microbial populations as well as qualitative changes in the number of Beta-glucuronidase producing microorganisms will be performed. These studies should provide: 1) a better understanding of the relationships among nutrition, microflora and colonic cancer; 2) nutritional linkage on the association between coronary heart disease and colonic cancer; 3) preliminary guidelines for studies in human nutrition and aimed at decreasing the incidence of colonic cancer and 4) an avenue for studies leading to a simple screening test identifying individuals who are subject to a greater risk of colonic carcinoma.